Abstract

The coronary vasodilator verapamil produced in isolated cat hearts an increase in coronary flow and a decrease in contractile force. Both effects occurred within a similar concentration range of the drug (2 x 10^-8 x 10^-7 M). The same concentrations of verapamil competitively antagonized calcium-induced contractions in strips of depolarized rabbit main pulmonary artery. Somewhat higher concentrations of the drug were required to inhibit contractions caused by norepinephrine in the polarized vessel. The inhibitory effect was not due to an interference with norepinephrine-induced depolarization of the vascular smooth muscle cells, as could be demonstrated with intracellular microelectrodes. In a nonvascular type of smooth muscle. the isolated nictitating membrane of the cat, verapamil also reduced the contractions caused by Ca⁺⁺ in depolarized and by norepinephrine in the polarized preparation. These observations are compatible with the view that the spasmolytic effect of verapamil in smooth muscle is due to a selective Ca⁺⁺-antagonistic effect of the drug. Such an action of verapamil does not seem to occur in adrenergic nerve terminals, since the drug did not influence the Ca⁺⁺-dependent release of norepincphrine from the isolated cat heart produced either by sympathetic nerve stimulation, by acetylcholine or by KCI.